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This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it.

SO153

Mental disorders as proteinopathies: from pilot evidence to DeSPERADo validation

MENTAL ILLNESSES AS PROTEINOPATHIES

A subset of patients with schizophrenia show an elevated serum 135 kDa NPAS3 signal, and peripheral protein aggregation is being tested as a candidate blood-based biomarker in a larger sample.

The study aims to investigate whether impaired proteostasis plays a role in schizophrenia (SCZ) and major depressive disorder (MDD), and whether peripheral blood carries aggregation-related signals. In the pilot phase, serum from 50 patients with SCZ, 50 patients with MDD, and 50 healthy controls underwent sequential solubilization; DISC1, dysbindin-1, NPAS3, TRIOBP-1, and CRMP1 were assessed by Western blot in whole serum and insoluble aggregate fractions. The 135 kDa NPAS3 signal was significantly higher in the SCZ group than in both controls and the MDD group (both comparisons were marked with ** on the poster), while the difference between controls and the MDD group was not significant (n.s.). Of the SCZ samples, 11/47 (23%) were aggregation-positive, and these patients had higher PANSS scores; dysbindin-1 and TRIOBP-1 were detected in the insoluble fraction, while mass spectrometry in the MDD proteomic analysis identified POTEF and vinculin as new candidate aggregated proteins. The ongoing DeSPERADo validation study aims to recruit 100 patients with SCZ, 100 patients with MDD, and 100 controls, alongside PANSS/HAM-D assessments and medication, comorbidity, and demographic data. To date, 92 patients with SCZ, 54 patients with MDD, and 47 controls have been enrolled, totaling 193/300 participants (64.3%). The validation workflow includes albumin depletion before fractionation, standardized sequential extraction and aggregate purification, total protein profiling, TCE staining, ubiquitination analysis, and Western blot detection, with results correlated with diagnosis, symptom severity, and treatment characteristics. The authors emphasize that peripheral protein aggregation signals could bridge molecular mechanisms and blood-based biomarker development, but that independent replication is essential.

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